Immunohistochemistry studies showed increased levels of STAT3 and IL-6, but low levels of programmed cell death protein 4 (PDCD4), in prostate tumor epithelial cells compared to adjacent perinormal prostate epithelial cells.
In this context, the anti-IL-6 antibody siltuximab (CNTO 328) has been demonstrated to inhibit growth of prostate tumors in vitro and in vivo and delays progression towards castration resistance.
Accelerated in vivo growth of prostate tumors that up-regulate interleukin-6 is associated with reduced retinoblastoma protein expression and activation of the mitogen-activated protein kinase pathway.
Our data provide evidence that IL6 may play a role in the growth of benign and malignant prostate tumors and suggest that the IL6 receptor could be a target for the delivery of therapeutic agents in prostate cancer.
Observations of the clinical behaviour of prostate tumors suggest that the increased secretion of IL-6 and CCL5 and the higher expression of PSMA may be correlated.
The present study examined the influence of paracrine IL-6 signaling on prostate tumor growth using allograft models of mouse prostate cancer (TRAMP-C2), colon cancer (MC38), and melanoma (B16) cell lines in wildtype (WT) and IL-6 knockout (IL-6<sup>-/-</sup> ) mice.
<b>Principal conclusions</b>: Taken together, our results argue that CXCL1 plays an important role in sustaining the growth of bladder and prostate tumors via up-regulation of IL6 and down-regulation of TIMP4.
Intriguingly, IL-6 inactivation restored the sensitivity to TGF-beta1-mediated growth arrest and apoptosis, suggesting that elevated IL-6 in advanced prostate tumors might act as a resistance factor against TGF-beta1.
Prostate tumor cell lines have been shown to both produce interleukin-6 (IL-6) and express the IL-6 receptor, suggesting a potential autocrine growth regulatory role for IL-6.
IL-6 can convert non-ALDH(high) cells to ALDH(high) cells in prostate cancer cell line as well as from cells derived from human prostate tumors, the conversion mediated by IL-6 was abrogated in the presence of STAT3 inhibitor or upon STAT3 knockdown.